Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice

Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3−/− mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3−/− mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3−/− mice. Lipid metabolism disorders in Sik3−/− mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice

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The inverse kinematics problem is formulated as a parameterized autonomous dynamical system problem, and respective analysis is carried out. It is shown that a singular point of work space can be mapped either as a critical or a noncritical point of the autonomous system, depending on the direction of approach to the singular point. Making use of the noncritical mapping, a closed-loop kinematic controller with asymptotic stability and velocity limits along degenerate singular or near-singular paths is designed. The authors introduce a specific type of motion along the reference path, the so-called natural motion. This type of motion is obtained in a straightforward manner from the autonomous dynamical system and always satisfies the motion constraint at a singular point. In the vicinity of the singular point, natural motion slows down the end-effector speed and keeps the joint velocity bounded. Thus, no special trajectory replannin